Wang Xiaowei, Lou Nanhong, Eberhardt Allison, Yang Yujia, Kusk Peter, Xu Qiwu, Förstera Benjamin, Peng Sisi, Shi Meng, Ladrón-de-Guevara Antonio, Delle Christine, Sigurdsson Björn, Xavier Anna L R, Ertürk Ali, Libby Richard T, Chen Lu, Thrane Alexander S, Nedergaard Maiken
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY 14642, USA.
Sci Transl Med. 2020 Mar 25;12(536). doi: 10.1126/scitranslmed.aaw3210.
Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified an ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve in rodents. β-amyloid (Aβ) was cleared from the retina and vitreous via a pathway dependent on glial water channel aquaporin-4 (AQP4) and driven by the ocular-cranial pressure difference. After traversing the lamina barrier, intra-axonal Aβ was cleared via the perivenous space and subsequently drained to lymphatic vessels. Light-induced pupil constriction enhanced efflux, whereas atropine or raising intracranial pressure blocked efflux. In two distinct murine models of glaucoma, Aβ leaked from the eye via defects in the lamina barrier instead of directional axonal efflux. The results suggest that, in rodents, the removal of fluid and metabolites from the intraocular space occurs through a glymphatic pathway that might be impaired in glaucoma.
尽管视网膜和视神经乳头具有高代谢活性,但缺乏传统的淋巴引流。我们在此确定了啮齿动物中通过近端视神经进行液体和废物清除的眼内类淋巴清除途径。β-淀粉样蛋白(Aβ)通过依赖于胶质水通道蛋白4(AQP4)的途径从视网膜和玻璃体清除,并由眼-颅压差驱动。穿过板层屏障后,轴突内的Aβ通过静脉周围间隙清除,随后引流至淋巴管。光诱导的瞳孔收缩增强了流出,而阿托品或升高颅内压则阻断了流出。在两种不同的青光眼小鼠模型中,Aβ通过板层屏障缺陷从眼内漏出,而不是通过定向轴突流出。结果表明,在啮齿动物中,眼内空间的液体和代谢产物通过类淋巴途径清除,而青光眼可能会损害该途径。